Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05013502 |
Other study ID # |
IRB-61538 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
November 15, 2021 |
Est. completion date |
June 30, 2023 |
Study information
Verified date |
July 2023 |
Source |
Stanford University |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Ascites is the most frequent complication of liver cirrhosis and results in increased
morbidity and mortality but current medical management options are limited. Here, the
investigators will conduct an interventional single-arm pilot clinical trial toevaluate the
feasibility of empagliflozin in managing diuretic-resistant ascites in patients with
decompensated cirrhosis. This single site, open label pilot study will enroll participants
with decompensated cirrhosis at a single site. Participants will receive empagliflozin 10mg
oral tablets once daily for 12 weeks with monitoring for safety and adverse events.
Description:
Pharmacologic options for the management of ascites are limited to diuretics only. Each year
approximately 10% of patients with cirrhosis develop diuretic-resistant ascites,
necessitating the use of more invasive procedures such a paracentesis, transjugular
intrahepatic portosystemic shunting (TIPS), and transplantation; each modality is associated
with significant risks and limitations. Patients treated with diuretics may also develop
complications such as acute kidney injury, encephalopathy, muscle cramping, or hyponatremia,
limiting optimal dosages of these medications and hence, resulting in inadequate control of
fluid retention. Thus, ascites that is resistant to our current therapies is an important
unmet medical need.
Recently, SGLT2-Is have been shown to reduce heart failure hospitalizations and
cardiovascular death in patients with and without diabetes in landmark, large-scale clinical
trials. Empagliflozin improved heart failure outcomes without altering hemoglobin A1c or
increasing risk of hypoglycemia in individuals without diabetes, suggesting that SGLT2-Is may
act through a neurohormonal mechanism independent of blood glucose changes. Because cirrhosis
and heart failure are disorders with a common pathophysiology of decreased effective arterial
blood volume with resultant stimulation of the renin-angiotensin-aldosterone system (RAAS),
sympathetic nervous system, and total body fluid overload, the investigators hypothesize that
SGLT2-Is may be effective in the management of ascites. Multiple lines of evidence suggest
SGLT2-Is may have a beneficial role in chronic liver disease. Several case reports of
patients with cirrhosis and diuretic-resistant ascites have found that SGLT2-I treatment was
associated with near resolution of ascites and pedal edema. SGLT2-I treatment has also
demonstrated improved hepatic function, reduction of fibrosis and normalization of liver
enzymes in non-alcoholic fatty liver disease (NAFLD).Although SGLT2-I are partially cleared
by the liver, empagliflozin is well tolerated in patients with cirrhosis. Thus, the
investigators initiated a feasibility study to test the hypothesis that the SGLT2-I,
empagliflozin, will decrease ascites by attenuating maladaptive neurohormonal and
inflammatory responses in cirrhosis.